Haimanot Wasse

Neighborhood poverty and racial disparities in kidney transplant waitlisting.

Racial disparities persist in the United States renal transplantation process. Previous studies suggest that the distance between a patients residence and the transplant facility may associate with disparities in transplant waitlisting. We examined this possibility in a cohort study using data for incident, adult ESRD patients (1998 to 2002) from the ESRD Network 6, which includes Georgia, North Carolina, and South Carolina. We linked data with the United Network for Organ Sharing (UNOS) transplant registry through 2005 and with the 2000 U.S. Census geographic data. Of the 35,346 subjects included in the analysis, 12% were waitlisted, 57% were black, 50% were men, 20% were impoverished, 45% had diabetes as the primary etiology of ESRD, and 73% had two or more comorbidities. The median distance from patient residence to the nearest transplant center was 48 mi. After controlling for multiple covariates, distance from patient residence to transplant center did not predict placement on the transplant waitlist. In contrast, race, neighborhood poverty, gender, age, diabetes, hypertension, body mass index, albumin, and the use of erythropoietin at dialysis initiation was associated with waitlisting. As neighborhood poverty increased, the likelihood of waitlisting decreased for blacks compared with whites in each poverty category; in the poorest neighborhoods, blacks were 57% less likely to be waitlisted than whites. This study suggests that improving the allocation of kidneys may require a focus on poor communities.

Treatment Center and Geographic Variability in Pre-ESRD Care Associate with Increased Mortality

Late referral of patients with chronic kidney disease is associated with increased morbidity and mortality, but the contribution of center-to-center and geographic variability of pre-ESRD nephrology care to mortality of patients with ESRD is unknown. We evaluated the pre-ESRD care of > 30,000 incident hemodialysis patients, 5088 (17.8%) of whom died during follow-up (median 365 d). Approximately half (51.3%) of incident patients had received at least 6 mo of pre-ESRD nephrology care, as reported by attending physicians. Pre-ESRD nephrology care was independently associated with survival (odds ratio 1.54; 95% confidence interval 1.45 to 1.64). There was substantial center-to-center variability in pre-ESRD care, which was associated with increased facility-specific death rates. As the proportion of patients who were in a treatment center and receiving pre-ESRD nephrology care increased from lowest to highest quintile, the mortality rate decreased from 19.6 to 16.1% (P = 0.0031). In addition, treatment centers in the lowest quintile of pre-ESRD care were clustered geographically. In conclusion, pre-ESRD nephrology care is highly variable among treatment centers and geographic regions. Targeting these disparities could have substantial clinical impact, because the absence of > or = 6 mo of pre-ESRD care by a nephrologist is associated with a higher risk for death.

Association of Initial Hemodialysis Vascular Access with Patient-Reported Health Status and Quality of Life

BACKGROUND Although the arteriovenous fistula (AVF) is the recommended form of vascular access for patients with ESRD, its impact on patient perception of health status, quality of life (QOL), or satisfaction is unknown. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS This study compared patient-reported health status and QOL scores and vascular access type among a national random sample of 1563 patients at dialysis initiation and day 60 of ESRD during 1996 to 1997. Patients were stratified into five categories: AVF at first dialysis and day 60 of ESRD, arteriovenous graft (AVG) at first dialysis and day 60, central venous catheter (CVC) at first dialysis and AVF at day 60, CVC at first dialysis and AVG at day 60, and CVC at first dialysis and day 60. RESULTS Ten percent (n = 154) of patients had an AVF, 21% (n = 326) had an AVG, and 69% (n = 1083) had a CVC at dialysis initiation; those who were most likely to use an AVF were white and male. After statistical adjustment, patients with persistent AVF use reported greater physical activity and energy, better emotional and social well-being, fewer symptoms, less effect of dialysis and burden of kidney disease, and better sleep compared with patients with persistent CVC use, whereas measures such as cognitive and sexual function did not differ by access type. CONCLUSIONS Compared with persistent CVC use, early persistent AVF use is associated with the perception of improved health status and QOL among patients with ESRD. Future longitudinal studies may help to clarify further the association between QOL and vascular access.

High-dose cholecalciferol reduces parathyroid hormone in patients with early chronic kidney disease: a pilot, randomized, double-blind, placebo-controlled trial

BACKGROUND Vitamin D deficiency contributes to secondary hyperparathyroidism, which occurs early in chronic kidney disease (CKD). OBJECTIVES We aimed to determine whether high-dose cholecalciferol supplementation for 1 y in early CKD is sufficient to maintain optimal vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] concentration ≥30 ng/mL) and decrease serum parathyroid hormone (PTH). A secondary aim was to determine the effect of cholecalciferol on blood pressure and serum fibroblast growth factor-23 (FGF23). DESIGN This was a double-blind, randomized, placebo-controlled trial. Forty-six subjects with early CKD (stages 2-3) were supplemented with oral cholecalciferol (vitamin D group; 50,000 IU/wk for 12 wk followed by 50,000 IU every other week for 40 wk) or a matching placebo for 1 y. RESULTS By 12 wk, serum 25(OH)D increased in the vitamin D group only [baseline (mean ± SD): 26.7 ± 6.8 to 42.8 ± 16.9 ng/mL; P < 0.05] and remained elevated at 1 y (group-by-time interaction: P < 0.001). PTH decreased from baseline only in the vitamin D group (baseline: 89.1 ± 49.3 to 70.1 ± 24.8 pg/mL; P = 0.01) at 12 wk, but values were not significantly different from baseline at 1 y (75.4 ± 29.5 pg/mL; P = 0.16; group-by-time interaction: P = 0.09). Group differences were more pronounced in participants with secondary hyperparathyroidism (group-by-time interaction: P = 0.004). Blood pressure and FGF23 did not change in either group. CONCLUSIONS After 1 y, this oral cholecalciferol regimen was safe and sufficient to maintain serum 25(OH)D concentrations and prevent vitamin D insufficiency in early CKD. Furthermore, serum PTH improved after cholecalciferol treatment, particularly in patients who had secondary hyperparathyroidism.

Efficacy and safety of a short course of very-high-dose cholecalciferol in hemodialysis

BACKGROUND Vitamin D deficiency is highly prevalent among hemodialysis patients, but little data exist in support of an optimal repletion regimen. OBJECTIVE The objective was to ascertain the efficacy of weekly very-high-dose cholecalciferol (vitamin D(3)) in correcting vitamin D insufficiency and deficiency in patients with stage 5D chronic kidney disease. DESIGN We conducted a prospective, double-blind, randomized controlled pilot study that compared placebo with very high doses of oral cholecalciferol for 3 wk (200,000 IU/wk) in hemodialysis patients. We examined the rate of correction of vitamin D insufficiency or deficiency and the effect of treatment on markers of mineral metabolism and routine laboratory variables. RESULTS Twenty-seven subjects received placebo, and 25 received cholecalciferol. The majority (94%) of subjects had serum 25-hydroxyvitamin D [25(OH)D] concentrations <30 ng/mL. Study groups were similar with respect to baseline clinical characteristics, with the exception of hemoglobin concentrations, which were lower in the cholecalciferol-treated group (P < 0.04). At follow-up, 90.5% of subjects treated with cholecalciferol achieved serum 25(OH)D concentrations ≥30 ng/mL in contrast to 13.6% of the placebo group. There were no significant changes in serum calcium, phosphate, or intact parathyroid hormone during the study. CONCLUSION Short-term, high-dose oral cholecalciferol treatment of vitamin D deficiency in hemodialysis patients appears to be effective and with no evidence of toxic effects. This trial was registered at clinicaltrials.gov as NCT00912782.

Arteriovenous fistula use is associated with lower cardiovascular mortality compared with catheter use among ESRD patients.

The arteriovenous fistula (AVF) is the recommended form of dialysis vascular access, however, limited studies suggest that AVF creation may result in increased cardiovascular stress and remodeling. To explore the contribution of vascular access type to cardiovascular‐related (CV) mortality, we analyzed USRDS Clinical Performance Measures data comprising 4854 patients that initiated dialysis between October 1, 1999–December 31, 2004. CV mortality included death from acute myocardial infarction, atherosclerotic heart disease, cardiomyopathy, arrhythmia, cardiac arrest or stroke. Risk of cardiovascular mortality during a 4‐year observation was analyzed by Cox‐regression methods with adjustments for demographic and co‐morbid conditions. AVF use was strongly associated with lower all‐cause and CV mortality. After adjustment for covariates, AVF use 90 days after dialysis initiation remained significantly associated with lower cardiovascular mortality [hazard ratio (HR) 0.69, p = 0.0004] compared with catheter use. These findings suggest that vascular access type influences cause‐specific mortality beyond that of infection, and support existing guidelines recommending the use of an AVF early in the course of chronic end‐stage renal disease therapy.

High-Output Heart Failure: How to Define It, When to Treat It, and How to Treat It

Although hemodialysis patients who initiate and maintain a permanent form of dialysis vascular access have improved all-cause and cardiovascular survival compared with those who use catheters, the presence of an arteriovenous fistula has been shown to have a short-term, adverse effect on cardiac function. Through its effect as a left-to-right extracardiac shunt, the arteriovenous fistula can increase cardiac workload substantially, and, in certain patients, result in a high-output state and resultant heart failure over time. Here we review the mechanisms by which dialysis arteriovenous access may promote the development of high-output cardiac failure in end-stage renal disease patients, describe risk factors for and the diagnosis of high-output heart failure, and suggest management strategies for patients who develop high-output heart failure.

Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease

Background/objectives:Vitamin D has anti-inflammatory and immune-regulating properties. We aimed to determine if high-dose cholecalciferol supplementation for 1 year in subjects with early chronic kidney disease (CKD) improved circulating markers of inflammation and immunity.Subjects/methods:In this double-blind, randomized, placebo-controlled trial, 46 subjects with early CKD (stages 2 and 3) were supplemented with oral cholecalciferol (50 000 IU weekly for 12 weeks followed by 50 000 IU every other week for 40 weeks) or a matching placebo for 1 year. Serum tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein-10 and neutrophil gelatinase-associated lipocalin were measured at baseline, 12 weeks and 1 year. Serum cathelicidin (LL-37) was measured at baseline and 12 weeks. An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide (LPS) and Pseudomonas aeruginosa.Results:By 12 weeks, serum MCP-1 decreased in the cholecalciferol group (66.2±2.5 to 60.8±2.6 pg/ml, group-by-time interaction P=0.02) but was not different from baseline at 1 year. Other markers of inflammation and immunity did not change. In vitro, LPS- and Pseudomonas-activated monocytes treated with 1,25(OH)2D3 had significantly less MCP-1 secretion compared with untreated cells.Conclusions:High-dose cholecalciferol decreased serum MCP-1 concentrations by 12 weeks in patients with early CKD, although the decrease was not maintained for the remainder of the year. In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes.

Racial and Gender Differences in Arteriovenous Fistula Use among Incident Hemodialysis Patients

Background: Arteriovenous fistula (AVF) use is reported to differ among racial and gender groups. We sought to identify risk factors associated with incident AVF and whether racial and gender differences in AVF use persist after controlling for these factors. Methods: We evaluated 28,712 incident adult hemodialysis patients (age ≧18) from five ESRD networks starting dialysis between June 1, 2005 and May 31, 2006. Data were obtained from the Center for Medicaid and Medicare Services 2728 form. Results: Incident AVF use was reported for 11% of black and 12% of white patients [OR = 0.89 (95% CI: 0.83, 0.96)], and for 9% of females and 13% of males [OR = 0.66 (0.62–0.71)]. After adjusting for facility clustering, blacks were as likely as whites to use an AVF [OR = 1.00 (0.92–1.09)], while gender differences persisted [OR = 0.64 (0.59–0.69)]. Compared to patients with no renal care prior to dialysis initiation, incident AVF use was 16-fold greater among those with ≧12 months of nephrology care [OR = 15.99 (13.25–19.29)], 9-fold greater among those with 6–12 months of care [OR = 9.00 (7.45–10.88)] and 7-fold greater among those with at least 6 months of care [OR = 7.13 (5.73–8.88)]. Conclusion: Racial, but not gender, differences in incident AVF use were eliminated after accounting for clustering within facilities.

Health status as a potential mediator of the association between hemodialysis vascular access and mortality

BACKGROUND It is unknown whether the selection of healthier patients for arteriovenous fistula (AVF) placement explains higher observed catheter-associated mortality among elderly hemodialysis patients. METHODS From the United States Renal Data System 2005-2007, we used proportional hazard models to examine 117 277 incident hemodialysis patients aged 67-90 years for the association of initial vascular access type and 5-year mortality after accounting for health status. Health status was defined as functional status at dialysis initiation and number of hospital days within 2 years prior to dialysis initiation. RESULTS Patients with catheter alone had more limited functional status (25.5 versus 10.8% of those with AVF) and 3-fold more prior hospital days than those with AVF (mean 18.0 versus 5.4). In the unadjusted model, the likelihood of death was higher for arteriovenous grafts (AVG) {Hazard ratio (HR) 1.20 [95% CI (1.16-1.25)], catheter plus AVF [HR 1.34 (1.31-1.38)], catheter plus AVG [HR 1.46 (1.40-1.52)] and catheter only [HR 1.95 (1.90-1.99)]}, compared with AVF (P < 0.001). The association attenuated -23.7% (95% CI -22.0, -25.5) overall (AVF versus all other access types) after adjusting for the usual covariates (including sociodemographics, comorbidities and pre-dialysis nephrology care) {AVG [HR 1.21 (1.17-1.26)], catheter plus AVF [HR 1.27 (1.24-1.30)], catheter plus AVG [HR 1.38 (1.32-1.43)] and catheter only [HR 1.69 (1.66-1.73)], P < 0.001}. Additional adjustment for health status further attenuated the association by another -19.7% (-18.2, -21.3) overall but remained statistically significant . CONCLUSIONS The observed attenuation in mortality differences previously attributed to access type alone suggests the existence of selection bias. Nevertheless, the persistence of an apparent survival advantage after adjustment for health status suggests that AVF should still be the access of choice for elderly individuals beginning hemodialysis until more definitive data eliminating selection bias become available.